Developer site: The content shown here is test data.

MyEClinic
MyEClinic
Health Dictionary AI Health Chat Find an Online Doctor
A serene Zen garden with raked sand and smooth stones, symbolising clarity and calm

Health Dictionary

Reliable, easy-to-read patient information on common medical conditions — written in plain language, free of jargon, and grounded in current evidence. Browse the most frequent diagnoses, understand what they mean for everyday life, and learn which steps and questions help you have a focused conversation with your doctor.

Back to skin conditions

Protein Z

Introduction

For other uses, see Z-gene.

Protein Z (PZ or PROZ) is a protein which in humans is encoded by the PROZ gene.[2][3]

Protein Z is a member of the coagulation cascade, the group of blood proteins that leads to the formation of blood clots. It is a gla domain protein and thus vitamin K-dependent, and its functionality is therefore impaired in warfarin therapy. It is a glycoprotein.

Physiology

Physiology

Although it is not enzymatically active, it is structurally related to several serine proteases of the coagulation cascade: factors VII, IX, X and protein C. The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid surfaces.

The main role of protein Z appears to be the degradation of factor Xa. This is done by protein Z-related protease inhibitor (ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades factor XI, but this reaction does not require the presence of protein Z.

In some studies, deficiency states have been associated with a propensity to thrombosis. Others, however, link it to bleeding tendency; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for thrombosis.

Genetics

Genetics

It is 62 kDa large and 396 amino acids long. The PROZ gene has been linked to the thirteenth chromosome (13q34).

It has four domains: a gla-rich region, two EGF-like domains and a trypsin-like domain. It lacks the serine residue that would make it catalytically active as a serine protease.

History

History

Protein Z was first isolated in cattle blood by Prowse and Esnouf in 1977,[4] and Broze & Miletich determined it in human plasma in 1984.[5]

Structure

Structure

Structural analysis of protein Z will allow better understanding of its function. The Ramachandran plot for protein Z indicates it will form alpha helices. The final structure, all alpha domain, was determined by x-ray diffraction. It consists of chain A and B, which are both helix-loop-helix motifs.[1]

References

References

  1. ↑ 1.0 1.1 PDB: 1LP1​: Högbom M, Eklund M, Nygren PA, Nordlund P (March 2003). “Structural basis for recognition by an in vitro evolved affibody”. Proc. Natl. Acad. Sci. U.S.A. 100 (6): 3191–6. doi:10.1073/pnas.0436100100. PMC 404300. PMID 12604795.
  2. ↑ Ichinose A, Takeya H, Espling E, Iwanaga S, Kisiel W, Davie EW (November 1990). “Amino acid sequence of human protein Z, a vitamin K-dependent plasma glycoprotein”. Biochem. Biophys. Res. Commun. 172 (3): 1139–44. doi:10.1016/0006-291X(90)91566-B. PMID 2244898.
  3. ↑ Sejima H, Hayashi T, Deyashiki Y, Nishioka J, Suzuki K (September 1990). “Primary structure of vitamin K-dependent human protein Z”. Biochem. Biophys. Res. Commun. 171 (2): 661–8. doi:10.1016/0006-291X(90)91197-Z. PMID 2403355.
  4. ↑ Prowse CV, Esnouf MP (1977). “The isolation of a new warfarin-sensitive protein from bovine plasma”. Biochem. Soc. Trans. 5 (1): 255–6. PMID 892175.
  5. ↑ Broze GJ, Miletich JP (April 1984). “Human Protein Z”. J. Clin. Invest. 73 (4): 933–8. doi:10.1172/JCI111317. PMC 425104. PMID 6707212.
External links